反应详情

温度

0 °C

A mixture of diethyl phosphite (700 g, 5.07 mmole), paraformaldehyde (190 g, 6.33 mole) and triethylamine (51.0 g, 0.50 mole) in toluene (2.8 L) is heated ca 2 hr at 85°-90° C., then under relux for ca 1 h. The resulting solution is cooled to ca. 0° C., and checked by NMR (CDCl3) for completion of the reaction (in-process control). Then p-toluenesulfonyl chloride (869 g, 4.56 mole) and triethylamine (718 g, 7.09 mole) are added with cooling (0°-10° C.). The resulting mixture is stirred at ca. 22° C. for 17-24 h and checked by NMR (CDCl3) for completion of the reaction (in-process control). The solids are removed by vacuum filtration. The filtrate is washed with water (2×) and dried over anhydrous magnesium sulfate. The solvent is evaporated in vacuo to give the title compound as an oil in 65-75% (1060-1225 g) yield. As an in-process control, NMR (CDCl3) is obtained and the product purity is assayed by HPLC C18 -35% CH3CN in KH2PO4 (0.02M)!. The purity of the product is typically 85-95%.

1. temperatureis heated ca 2 hr at 85°-90° C.
2. waitunder relux for ca 1 h
3. customchecked by NMR (CDCl3) for completion of the reaction (in-process control)
4. temperaturewith cooling (0°-10° C.)
5. customchecked by NMR (CDCl3) for completion of the reaction (in-process control)
6. customThe solids are removed by vacuum filtration
7. washThe filtrate is washed with water (2×)
8. dry with materialdried over anhydrous magnesium sulfate
9. customThe solvent is evaporated in vacuo